The blood cells in paroxysmal nocturnal hemoglobinuria (PNH) possess an abnormal plasma membrane which is more susceptible to the hemolytic action of complement than is the plasma membrane of normal cells. The fixation of the third component of complement is increased and the terminal complex (C5b-9) is more efficient in effecting lysis. We propose to investigate the excessive fixation of C3 by investigation of the increased enzymatic activity of the alternative pathway C3 convertase complex (C3bBb) when present upon a PNH cell. We propose to investigate the interaction of this complex with control proteins of serum, Beta1H and C3b inactivator. The activity and stability of the classical pathway convertase (C4bC2a) on normal and PNH red cells will also be investigated. The activity of both C5 convertase complexes (C3bBbC3bn and C4b2aC3bn) in the activation and fixation of C5 will be investigated. The kinetic parameters (Km, Vmax, etc.) of these enzymes will be investigated. In order to understand the great susceptibility of the PNH membrane to the membrane attack complex (C5b-9), the polymeric structure of these complexes in the membrane of PNH, normal, and AET-treated normal red cells following reaction with complement will be investigated. The presence of a structure in the normal membrane capable of interacting with monomeric C5b-9 complexes to prevent their polymerization will be sought. By these investigations, we hope to be able to understand the abnormalities which lead to the clinical manifestations of PNH and the mechanism by which normal red cells are able to protect themselves from attack by complement.